tbuckley/cabot-search huggingface dataset:
Abstract P2-23-19: Interrogating multicellular signaling in breast cancer using a bio-orthogonal chemistry-based proteomics platform
Authors: Brad A. Krajina, Ami Yamamoto, Kevin J. Cheung, Samuel Madasu
Journal: Cancer Research (2023)

Abstract Tumors are multicellular ecosystems that communicate through the exchange of extracellular signaling molecules. In breast cancer, this multicellular communication can enable tumor cells to cooperate in a range of contexts, including tumor invasion and the outgrowth of distal metastases. Illuminating the mechanisms by which tumor cells communicate may reveal new therapies. To this end, three-dimensional tumor organoid models have emerged as versatile platforms for modeling multicellular behavior ex vivo. However, organoid culture typically requires the use of poorly defined, animal-derived extracellular matrices, such as Matrigel. These exogenous matrices contain thousands of proteins that dominate over and conceal cell-secreted factors in conventional proteomics approaches. Revealing low abundance cell-secreted factors from this complex exogenous background presents a formidable challenge. To surmount this challenge, we develop a new method to isolate the pericellular proteome in 3D organotypic culture models. This technology harnesses biorthogonal click chemistry to bypass exogenous factors, infiltrate intercellular spaces, and retrieve the endogenous intercellular proteome. This approach requires no genetic manipulation, requires only 1 million cells, and can be adapted to diverse organotypic models. These capabilities enable isolation of intercellular signaling factors in models that yield precious amounts of material and that can sustain only limited manipulation ex vivo, which we demonstrate using organoids established from patient-derived xenografts. To establish the generalizability of our approach, we apply this technology to a panel of breast cancer and small-cell lung cancer organoid models. Furthermore, we demonstrate that this method can be readily adapted to different extracellular matrix environments that are widely employed in organoid research, including basement membrane matrices and collagen gels. Taken together, our results establish this technology as a scalable and generalizable platform that may open opportunities for researchers investigating diverse questions in organoid models of cancer. Moving forward, we are leveraging these capabilities to investigate changes in the intercellular proteome that emerge after the acquisition of therapy resistance. We hope to uncover new mechanisms of collective signaling that may be targeted to overcome therapy resistance. Citation Format: Brad A. Krajina, Ami Yamamoto, Kevin J. Cheung, Samuel Madasu. Interrogating multicellular signaling in breast cancer using a bio-orthogonal chemistry-based proteomics platform [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-19.
Abstract P1-08-02: Implementation of Integrative Medicine Program for Breast Medical Oncology Professionals in an Academic Cancer Center
Authors: W. Iris Zhi, Rui Wanq, Ting Bao
Journal: Cancer Research (2023)

Abstract BACKGROUND: Integrative medicine such as acupuncture, meditation, yoga and massage are highly desired by breast cancer survivors. Breast medical oncology professionals including physicians, advanced nurse practitioners and physician assistants are often the first clinicians that patients would expect to discuss the use of integrative medicine. Many distressing symptoms, such as hot flashes, insomnia, anxiety, and pain, are common and remain challenging to manage with limited pharmacological intervention available and potential toxicities. Evidence-based integrative medicine approaches, including acupuncture, meditation, yoga, and massage, may help reduce this symptom burden and improve quality of life. However, many breast medical oncology professions are not familiar with current evidence and knowledge in integrative medicine. Therefore, there is an urgent need to educate them on the fundamentals of evidence-based integrative medicine interventions that could improve quality of life for breast cancer survivors. METHODS: We designed the Integrative Oncology training Program for breast medicine professionals at our institution. The program faculty are composed of five breast medical oncologists, five integrative medicine faculty, and one education coordinator. RESULTS: We developed an online, interdisciplinary five-hour course on evidence-based integrative oncology with essential knowledge on integrative medicine approaches for breast cancer survivors. We determined the topic of interest based on feedback from the program faculty. The integrative medicine approaches in management of hot flashes, arthralgia, insomnia, are cannabis uses are some examples that were highly in-demand. The program summarizes high-quality evidence in herbal supplements, acupuncture, meditation, and yoga, pertinent to the audience, as well as the referral flow to our Integrative Medicine Service. CONCLUSIONS: Integrative medicine education programs for oncological professionals are needed to disseminate integrative medicine knowledge and to prepare them to guide our patients on integrative and complementary approaches during and after anticancer treatments. Citation Format: W. Iris Zhi, Rui Wanq, Ting Bao. Implementation of Integrative Medicine Program for Breast Medical Oncology Professionals in an Academic Cancer Center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-08-02.
Abstract OT1-12-04: MRO PMS study - Intraoperative Specimen Magnetic Resonance Imaging System for Intraoperative Margin Assessment for Invasive Breast Cancer Using the ClearCoast™ System in Breast Conserving Surgery
Authors: Marc Thill, Katharina Kelling, Viviane van Haasteren, Tina Schnitzbauer, Petia Kiene, Anna Levin, Eyal Kolka, Zachi Peles, Sebastian Aulmann
Journal: Cancer Research (2023)

Abstract Background Re-operation for involved margins in breast conserving surgery is associated with worse cosmetic outcome, increased medical costs, and patient anxiety. Therefore, obtaining negative margins during primary BCS is essential. In our prior non-interventional study, published in October 2021 (Thill M et al., J Surg Oncol 2021) the re-operation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% re-operations, if results had not been blinded for the surgeon. The results suggested a potential reduction of the re-operation rate by up to 80% for patients undergoing BCS. Aim of the study Aim of our current study is to evaluate the interventional performance of the ClearCoast™ system (ClearCut Medical, Ltd.) in assessing surgical margins for IBC in breast conserving surgery (BCS) and reducing the re-excision rates. Material and Methods The ClearCoast™ system utilizes a diffusion-weighted-imaging (DWI) protocol to create 2D surface maps showing T2*, a MR parameter related to the tissue’s apparent diffusion coefficient (ADC), with a depth penetration of 1mm. ADC is a highly accurate differentiator for irregular versus normal tissue. From May 2021 till to date a prospective, non- blinded post marketing study (N=93), evaluating the performance of the ClearCoast™ system is currently ongoing in the Breast Centre at the AGAPLESION MARKUS KRANKENHAUS, Frankfurt, Germany. After standard evaluation with ultrasound and/or X-ray with or without wire or clip marking, the specimens are intraoperatively scanned with the ClearCoast™ system, and positive margins will lead to a direct re-resection by decision of the surgeon applying a simple T2* threshold to flag irregular tissue. The final histopathology results will be compared with the scan results on a margin per margin bases. In addition, the rates of recurrent surgery of the interventional group will be compared with those of a historical group on the bases of matched pairs. Primary endpoint of the study is the re-excision rates in both the interventional and the historical standard of care group. To date, 64 patients are enrolled in the trial, therefore, results of the trial may be presented at the SABCS 2022. Citation Format: Marc Thill, Katharina Kelling, Viviane van Haasteren, Tina Schnitzbauer, Petia Kiene, Anna Levin, Eyal Kolka, Zachi Peles, Sebastian Aulmann. MRO PMS study - Intraoperative Specimen Magnetic Resonance Imaging System for Intraoperative Margin Assessment for Invasive Breast Cancer Using the ClearCoast™ System in Breast Conserving Surgery [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-04.
Abstract P2-21-11: A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model
Authors: Rizwan Ali, Sarah Huwaizi, Arwa Alsubait, Mohamed Boudjelal
Journal: Cancer Research (2023)

Abstract The desired effect of cancer therapeutics can only be conceived when applied to complex multicellular structures with different cell types and extracellular matrix (ECM) in three-dimensional (3D) space. Therefore, 3D cell culture systems have become very popular in drug screening and discovery. There is an immense demand for highly efficient and easy methods to produce 3D spheroids in any cell format. However, heterogeneity in size, extended cultivation times, and reproducibility for high throughput assays are limiting factors in the generation of spheroids. Recently we have established a naturally transformed breast cancer cell line, KAIMRC1 (1), from ductal breast carcinoma. We have developed a novel and easy method to produce spheroids (2) from KAIMRC1 cells in vitro, which can be used as a 3D model to study proliferation, differentiation, metabolism, cell death, and drug response of cells in the tumor microenvironment. We developed an in-vitro high content imaging (HCI) based cellular assay using commercially available compound panels to perform initial drug screening in the KAIMRC1 spheroids model. Our approach allows rapid screening of a panel of drugs to assess inhibitory effects on the growth of tumor cells in 3D cultures. To mimic the actual in-vivo tumor microenvironment, we are now developing an HCI-based assay utilizing 3D KAIMRC1 spheroids co-cultured with patient-derived fibroblast cells. 1. Ali, Rizwan, et al. “Isolation and Characterization of a New Naturally Immortalized Human Breast Carcinoma Cell Line, KAIMRC1.” BMC Cancer 17 (2017) 2. Rizwan Ali et al., (2021) New Born Calf Serum (NBCS) can induce spheroid formation in breast cancer KAIMRC1 cell line. Front. Mol. Biosci. DOI: 10.3389/fmolb.2021.769030 Citation Format: Rizwan Ali, Sarah Huwaizi, Arwa Alsubait, Mohamed Boudjelal. A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-21-11.
Abstract ED6-1: Contralateral mastectomy in patients with germline mutations
Authors: Katharine Yao
Journal: Cancer Research (2023)

Abstract The educational session titled "Contralateral mastectomy in patients with germline mutations" will cover contralateral mastectomy in affected gene carriers. The session will first cover trends in contralateral mastectomy in germline mutation carriers and the impact of genetic testing on contralateral mastectomy utilization. Second, the session will review guidelines on contralateral mastectomy for gene carriers. Literature on potential beneficial impacts of contralateral mastectomy for gene carriers will be reviewed. Impact to contralateral risk, survival outcomes and patient quality of life will be examined. Lastly, the session will review new surgical approaches for prophylactic mastectomy and protocols to reduce pain and enhance recovery after mastectomy. Citation Format: Katharine Yao. Contralateral mastectomy in patients with germline mutations [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED6-1.
Abstract P2-25-04: Granzyme B expression in tumor microenvironment as a biomarker for prognosis of triple-negative breast cancer
Authors: Kimihisa Mizoguchi, Masafumi Nakamura
Journal: Cancer Research (2023)

Abstract Background: Many analyzes on tumor microenvironment has made it clear that tumor infiltrating lymphocytes (TILs) plays an important role in treating cancers with high tumor mutation burden such as triple-negative breast cancer (TNBC). We reported that the relationship between TILs and PD-L1 expression (Oncotarget 2017) and revealed that high-TILs/positive-PD-L1 expression population in TNBC was associated with better prognosis. However, its molecular mechanism is still unclear. Meanwhile, it was well-known that activated T-cells work as antitumor lymphocytes by enhancing the apoptosis by granzyme B (GZMB) and perforin, and then production of cytokines such as INFγ. We focused on GZMB and examined the function of activated T-cells. Patients and Methods: This study included 230 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at our three hospitals between January 2004 and December 2014. The immunohistochemistry (IHC) scoring for GZMB expression on TILs was defined as 1 or 5%. PD-L1 positivity was defined as ≥ 10 Combined Positive Score (CPS) based on tumor and immune cells staining positive for PD-L1. Results: Of the 230 TNBC, GZMB on TILs was expressed as more than 1% and 5% positive in 181 (79%) and 50 (22%) tumors, respectively, and PD-L1 and CD8 on TILs was expressed as positive in 99 (43%) and 127 (55%) tumors, respectively. GZMB expression (more than 5%) was significantly correlated with PD-L1 expression (P=0.0048) and CD8 expression (P=0.0156). There was no significant difference in recurrence free survival (RFS) and overall survival (OS) regardless of CD8 or PD-L1expression level. Meanwhile, the patients with GZMB-positive tumors had a longer OS, compared to the patients with GZMB-negative tumors (P = 0.0155 in RFS and P = 0.0202 in OS) when PD-L1 expression on TILs was high, but not when it was low. Conclusion: OS was significantly longer among patients with high GZMB expressing TNBC. These results may validate the significance of GZMB as a biomarker for various immunotherapies in TNBC. Citation Format: Kimihisa Mizoguchi, Masafumi Nakamura. Granzyme B expression in tumor microenvironment as a biomarker for prognosis of triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-25-04.
Abstract CC1-2-1: Duration of endocrine therapy
Authors: Eleftherios (Terry) Mamounas, Kathryn Ruddy
Journal: Cancer Research (2023)

Abstract Patients with hormone-receptor positive, early-stage breast cancer are at considerable risk for late recurrence. Previous randomized clinical trials have shown that extending adjuvant tamoxifen to ten vs. five years improves disease-free survival (and overall survival in one trial). Adding five years of an aromatase inhibitor (AI) after five years of tamoxifen has also been shown to significantly improve disease-free survival in postmenopausal patients. Benefit from extending adjuvant AI therapy beyond five years in patients who have received five years of an AI or tamoxifenàAI has also been recently demonstrated in several clinical trials but the absolute benefit appears small and the ideal duration of the extended therapy is still a topic of debate. Over the past decade, efforts have focused on identifying predictors of risk of late recurrence and predictors of benefit from extended endocrine therapy. Clinicopathologic factors and circulating tumor cells can predict risk of late recurrence but not benefit from extended ET. Several commercially available genomic classifiers can further stratify risk of late recurrence, and some have also been found to predict benefit from extended ET. Their clinical utility for tailoring the use of extended endocrine therapy continues to evolve. Citation Format: Eleftherios (Terry) Mamounas, Kathryn Ruddy. Duration of endocrine therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr CC1-2-1.
Abstract P1-03-03: Real-World Treatment Patterns and Clinical Outcomes in Patients Treated with Eribulin After Prior PI3K Inhibitor Therapy for Metastatic Breast Cancer
Authors: Ravi K. Goyal, Jingchuan Zhang, Keith L. Davis, Peter A. Kaufman
Journal: Cancer Research (2023)

Abstract Background: Eribulin has been used in the treatment of metastatic breast cancer (MBC) following approval in 2010 in the United States (US). Recently, several new therapeutic classes have been approved for patients with MBC, including the phosphoinositide 3-kinase (PI3K) inhibitor alpelisib. This study aimed to assess the treatment patterns and clinical outcomes in patients with MBC treated with eribulin following alpelisib in US clinical practice. Methods: A retrospective, noninterventional medical chart review study was performed to obtain de-identified patient data via participating oncologists. Study population included adult female patients with a diagnosis of MBC who initiated eribulin therapy between March 1, 2019, and September 30, 2020, following prior therapy with alpelisib. Eribulin treatment parameters and patient characteristics were captured. Progression-free survival (PFS) and overall survival (OS) since eribulin initiation was assessed using Kaplan-Meier methods. Results: This interim analysis included 47 eligible patients (median age 62 years at eribulin initiation; 77% Caucasian). The majority (91.5%) of this cohort had HR+/HER2– MBC; 72.3% had a known PIK3CA mutation. Eribulin was classified as 2nd line, 3rd line, and 4th line or later in 34%, 47%, and 19% of patients, respectively, in regard to the line of therapy in the metastatic setting. At last follow-up, eribulin treatment was ongoing for 34% of patients. The median treatment duration was 5.2 months (q1, q3: 3.9, 7.1) among those who had discontinued eribulin, and 11.3 months (q1, q3: 10.0, 13.7) among those who were still on treatment. At last follow-up, 72.3% of patients were alive. The estimated PFS rate at 12 months was 57.1% (95% CI: 40.0-70.9). Median was not reached for OS after initiation of eribulin; the estimated OS rates at 12 and 24 months were 80.2% (95% CI: 65.3-89.2) and 61.8% (95% CI: 37.2-79.2), respectively. Conclusion: Among patients with MBC who initiated eribulin following prior treatment with a PI3K inhibitor, over 60% were estimated to survive for at least 2 years. Future studies to confirm these results are warranted. Citation Format: Ravi K. Goyal, Jingchuan Zhang, Keith L. Davis, Peter A. Kaufman. Real-World Treatment Patterns and Clinical Outcomes in Patients Treated with Eribulin After Prior PI3K Inhibitor Therapy for Metastatic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-03-03.
Abstract ED6-2: RT: How short can it be
Authors: David Krug
Journal: Cancer Research (2023)

Abstract Adjuvant whole-breast radiotherapy for breast cancer has traditionally been delivered over the course of 5 weeks. In the past decades, there has been a paradigm shift towards moderate hypofractionation with 15-16 fractions over 3 weeks based on randomized controlled trials demonstrating comparable oncological safety, decreased acute toxicity and similar long-term toxicity compared to conventional fractionation. More recently, ultra-hypofractionated whole-breast radiotherapy delivered with 5 fractions over 1 week or 5 weeks has been introduced into the clinic. Furthermore, the increasing use of partial-breast irradiation with a de-escalation of the target volume to the region of the lumpectomy cavity has further allowed acceleration of radiotherapy delivery for patients with breast cancer. This lecture will summarize recent advances and data on hypofractionation for breast cancer. Citation Format: David Krug. RT: How short can it be [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED6-2.
Abstract ED13-1: Beyond anthracyclines and trastuzumab: Cardiotoxicity of novel agents
Authors: Susan Dent
Journal: Cancer Research (2023)

Abstract Breast cancer treatment can have a diverse array of delayed and long-term effects, including cardiovascular events such as heart failure, valvular damage, coronary artery disease, arrythmias, and cardiac dysfunction. The adverse cardiovascular effects of anthracyclines and trastuzumab in the treatment of early and advanced breast cancer have been well elucidated withing the literature; however, there is less understanding of the potential cardiovascular impact of more recent novel breast cancer therapies. Dual HER2 targeted therapy (pertuzumab/trastuzumab) is now standard of care for neoadjuvant and adjuvant treatment, particularly in the setting of lymph node involvement, but is there a higher risk of cardiotoxicity? There is a limited understanding of the potential short- and long-term cardiovascular toxicity associated with antibody-drug conjugates, such as T-DM1 and fam-trastuzumab deruxtecan, and well as oral anti-HER2 tyrosine kinase inhibitors such as lapatinib, neratinib, and more recently tucatinib. CDK4/6 inhibitors (eg ribociclib) combined with endocrine therapy have significantly improved clinical outcomes for individuals with hormone receptor positive, HER-2 advanced breast cancer but are associated with an increased risk of QTc prolongation, which can be compounded by electrolyte abnormalities and drug-drug interactions. Immune checkpoint inhibitors (pembrolizumab) are approved in the neoadjuvant (high risk) and advanced setting (PDL-1 positive) for triple negative breast cancer but are associated with several toxicities including endocrinopathies and rarely fatal myocarditis. The goal of this session is to improve the awareness and understanding of the potential cardiovascular toxicities associated with modern anti-cancer therapies used in the treatment of breast cancer. Citation Format: Susan Dent. Beyond anthracyclines and trastuzumab: Cardiotoxicity of novel agents [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED13-1.